Abstract
The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men and the second most deadly
Since Asian men who immigrate to Western countries acquire an increased risk of PCa [2], environmental exposures likely contribute to prostate carcinogenesis in these men
After two weeks of consumption of PhIP-containing diets, the body weights in the PhIP-alone and tomato + broccoli + PhIP groups significantly diverged from control rats (p,0.0004), but did not differ significantly from each other (p = 0.052, Figure 2)
Summary
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men and the second most deadly. Since Asian men who immigrate to Western countries acquire an increased risk of PCa [2], environmental exposures likely contribute to prostate carcinogenesis in these men. One welldocumented difference in the diets of men from these two cultures is that Westerners consume higher quantities of meat [4,5,6,7]. Heterocyclic amines are formed upon cooking meats at high temperatures, and a number of these compounds are potent carcinogens in rats. Exposure to 2-amino-1-methyl6-phenylimidazo[4,5-b]pyridine (PhIP), the primary heterocyclic amine produced from cooking meat, results in cancer of the prostate, intestine, and mammary gland of rats [8,9,10,11,12]. Americans consume approximately 13.4 ng/kg/day of heterocyclic amines from well-cooked meats, with seventy percent being PhIP [13]. PCa death rates have been dropping in both Caucasians and African-Americans, the rates for African-Americans are still more than double [18] that of Caucasians, possibly due in part to increased PhIP consumption in this demographic group [13,17,19,20]
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